Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs.

Padhye S, Ahmad A, Oswal N, Sarkar FH - J Hematol Oncol (2009)

Bottom Line:
Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities.We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol.The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent.

ABSTRACTGarcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent.

Mentions:
Saxena and coworkers grafted chalcone derivatives on estradiol framework some of which showed potent anticancer activity against some human cancer cell lines [87]. Thus, compounds B and C in Figure 4 show potent activity against estrogen receptor-positive and hormone-dependent human breast cancer cell lines, MCF-7. Chalcone A was further modified to yield corresponding indanone derivative (C) using the Nazarov reaction, which showed better activity than the parent compound against MCF-7 breast cancer cell line. Active anticancer derivatives were also evaluated for osmotic hemolysis using the erythrocyte as a model system. It was observed that chalcone derivatives showing cytotoxicity against cancer cell lines did not affect the fragility of erythrocytes and hence may be considered as non-toxic to normal cells; however, further research in this area is urgently needed. Nitric oxide production by trimethoxy chalcone derivatives, with various patterns of fluorination, has also been evaluated [88]. One of this compounds, 2, 4, 6-trimethoxy-20-trifluoromethylchalcone, inhibited the production of NO and prostaglandin E2 in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. The inhibition (76.3% inhibition at 10 μM concentration) was dose-dependent without any evidence of a cytotoxic effect. It was suggested that NO reduction was a consequence of inhibition of the expression PGE2 accumulation. The fluorinated chalcones tested by Nakamura et al. showed 5-lipoxygenase inhibition on rat basophilic leukemia-1 (RBL-1) cells and inhibitory action on Fe3+-ADP induced NADPH-dependent lipid peroxidation in rat liver microsomes [89]. The potencies were comparable or better than those of the lead compound, viz. 3,4-dihydroxychalcone. The structure of fluorinated chalcone is presented in Figure 5.

Mentions:
Saxena and coworkers grafted chalcone derivatives on estradiol framework some of which showed potent anticancer activity against some human cancer cell lines [87]. Thus, compounds B and C in Figure 4 show potent activity against estrogen receptor-positive and hormone-dependent human breast cancer cell lines, MCF-7. Chalcone A was further modified to yield corresponding indanone derivative (C) using the Nazarov reaction, which showed better activity than the parent compound against MCF-7 breast cancer cell line. Active anticancer derivatives were also evaluated for osmotic hemolysis using the erythrocyte as a model system. It was observed that chalcone derivatives showing cytotoxicity against cancer cell lines did not affect the fragility of erythrocytes and hence may be considered as non-toxic to normal cells; however, further research in this area is urgently needed. Nitric oxide production by trimethoxy chalcone derivatives, with various patterns of fluorination, has also been evaluated [88]. One of this compounds, 2, 4, 6-trimethoxy-20-trifluoromethylchalcone, inhibited the production of NO and prostaglandin E2 in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. The inhibition (76.3% inhibition at 10 μM concentration) was dose-dependent without any evidence of a cytotoxic effect. It was suggested that NO reduction was a consequence of inhibition of the expression PGE2 accumulation. The fluorinated chalcones tested by Nakamura et al. showed 5-lipoxygenase inhibition on rat basophilic leukemia-1 (RBL-1) cells and inhibitory action on Fe3+-ADP induced NADPH-dependent lipid peroxidation in rat liver microsomes [89]. The potencies were comparable or better than those of the lead compound, viz. 3,4-dihydroxychalcone. The structure of fluorinated chalcone is presented in Figure 5.

Bottom Line:
Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities.We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol.The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent.

ABSTRACTGarcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent.